Anhydride modified cantharidin analogues useful in the treatment of cancer

Abstract

Anhydride modified cantharidin analogues useful in the treatment of certain forms of cancer also methods for the screening for anti-cancer activity of these analogues and/or their ability to sensitise cancer cells to cancer treatment. The modified cantharidin analogues have structure (I) or (II), wherein R 1 , R 2 , R 3 and R 4 are H, aryl or alkyl; X is O, N or S; Y is O, S, NH, NR; R is alkyl or aryl; A and B are H or CH 3 ; W and Z are CHOH or C═O. These compounds inhibit protein phosphatase.

1 . A cell permeable inhibitor of protein phosphatase, said inhibitor being an anhydride modified cantharidin analogue.  
   
   
       2 - 3 . (canceled)  
   
   
       4 . A compound of the formula:  
     
       
         
         
             
             
         
       
     
     wherein R 1  and R 2  are H, aryl or alkyl; X is O, N or S; Y is O, S, SR, NH, NR, CH 2 OH, CH 2 OR; R is alkyl or aryl; A and B are H or CH 3 ; W and Z are CHOH or C=0 and R 1  and R 2  can cyclise to form a ring as follows:  
     
       
         
         
             
             
         
       
     
     wherein R 3  and R 4  are H, aryl or alkyl.  
   
   
       5 - 12 . (canceled)  
   
   
       13 . A method of treating cancer which method comprises administering to a patient in need of such treatment, an effective amount of an inhibitor according to any one of  claims 1  to  3  or a compound according to any one of  claims 4  to  6 , together with a pharmaceutically acceptable carrier, diluent and/or excipient.  
   
   
       14 . A method according to  claim 13 , wherein the cancer is inherently resistant to conventional chemotherapy.  
   
   
       15 . A method according to  claim 13  or  claim 14 , wherein the cancer is colon cancer or non small-cell lung cancer.  
   
   
       16 . A method according to any one of  claims 13  to  15 , wherein the inhibitor or the compound is administered intravenously.  
   
   
       17 - 29 . (canceled)